Trastuzumab deruxtecan (T-DXd) is a HER2-targeting antibody-drug conjugate is approved by the US FDA for patients with advanced HER2-positive metastatic breast cancer based on the results from DESTINY-Breast01 (NCT03248492). Javier Cortés, MD, PhD, Vall d’Hebron University Hospital, Barcelona, Spain, presents the practice-changing results of DESTINY-Breast03 study (NCT03529110), a Phase III trial comparing the efficacy and safety of T-DXd versus trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival vs T-DM1 in this patient population with manageable toxicity. This interview took place at the European Society for Medical Oncology (ESMO) 2021 congress.